The effects of 2-aminoethoxydiphenyl borate, a novel inositol 1,4,5-trisphosphate receptor modulator on myometrial contractions

These studies were performed to evaluate the effect of 2-aminoethoxydipheny l berate (2-APB), a novel membrane-permeable inositol 1,4,5-trisphosphate-r eceptor inhibitor on agonist-induced, spontaneous, and KCl-stimulated in vi tro myometrial contractions. 2-APB significantly inhibited spontaneous myom etrial contractions as well as phasic contractions induced by various utero tonic agonists. Confiriming its effects on intracellular calcium release, 2 -APB inhibited phasic contractions in the absence of extracellular calcium. 2-APB had little effect on the tonic response to KCl stimulation, implicat ing its insignificant effect on voltage-gated calcium channels. The inhibit ory effect of 2-APB on phasic contractions was completely reversed by washo ut. In summary, 2-APB effectively penetrated uterine tissue and significant ly inhibited myometrial events previously shown to be mediated through acti vation of the PI-signaling pathway. (C) 1999 Academic Press.